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PMID: 12589041 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Dendritic fibroblasts in three-dimensional collagen matrices.

Molecular biology of the cell ·Vol. 14 ·No. 2 ·2003-02-00 ·Pages 384-95

Grinnell F, Ho CH, Tamariz E, Lee DJ, Skuta G

Abstract

Cell motility determines form and function of multicellular organisms. Most studies on fibroblast motility have been carried out using cells on the surfaces of culture dishes. In situ, however, the environment for fibroblasts is the three-dimensional extracellular matrix. In the current research, we studied the morphology and motility of human fibroblasts embedded in floating collagen matrices at a cell density below that required for global matrix remodeling (i.e., contraction). Under these conditions, cells were observed to project and retract a dendritic network of extensions. These extensions contained microtubule cores with actin concentrated at the tips resembling growth cones. Platelet-derived growth factor promoted formation of the network; lysophosphatidic acid stimulated its retraction in a Rho and Rho kinase-dependent manner. The dendritic network also supported metabolic coupling between cells. We suggest that the dendritic network provides a mechanism by which fibroblasts explore and become interconnected to each other in three-dimensional space.

MeSH Terms
Actins/metabolism Blood Platelets/metabolism Cell Adhesion Cell Movement Cells, Cultured Collagen/metabolism Cytoskeleton/metabolism Dendrites/metabolism Extracellular Matrix/metabolism Fibroblasts/metabolism Humans Intracellular Signaling Peptides and Proteins Lysophospholipids/metabolism Microscopy, Fluorescence Microtubules/metabolism Platelet-Derived Growth Factor/metabolism Protein Serine-Threonine Kinases/metabolism Time Factors rho-Associated Kinases
Chemicals
Actins Intracellular Signaling Peptides and Proteins Lysophospholipids Platelet-Derived Growth Factor Collagen Protein Serine-Threonine Kinases rho-Associated Kinases
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Grinnell Frederick
Department of Cell Biology, University of Texas Southwestern Medical School, Dallas 75390-9039, USA. frederick.grinnell@utsouthwestern.edu
Ho Chin-Han
Tamariz Elisa
Lee David J
Skuta Gabriella
References (67)
67 references, click to expand
  1. Cell migration: a physically integrated molecular process.
    Cell. 1996 Feb 9;84(3):359-69 PMID: 8608589
  2. Actin-based cell motility and cell locomotion.
    Cell. 1996 Feb 9;84(3):371-9 PMID: 8608590
  3. Focal adhesions, contractility, and signaling.
    Annu Rev Cell Dev Biol. 1996;12:463-518 PMID: 8970735
  4. Development and differentiation of dermal cells in man.
    J Invest Dermatol. 1978 Jul;71(1):2-8 PMID: 355564
  5. Production of a tissue-like structure by contraction of collagen lattices by human fibroblasts of different proliferative potential in vitro.
    Proc Natl Acad Sci U S A. 1979 Mar;76(3):1274-8 PMID: 286310
  6. Fibroblast traction as a mechanism for collagen morphogenesis.
    Nature. 1981 Mar 19;290(5803):249-51 PMID: 7207616
  7. Microtubule growth activates Rac1 to promote lamellipodial protrusion in fibroblasts.
    Nat Cell Biol. 1999 May;1(1):45-50 PMID: 10559863
  8. Regulation of LPA-promoted myofibroblast contraction: role of Rho, myosin light chain kinase, and myosin light chain phosphatase.
    Exp Cell Res. 2000 Feb 1;254(2):210-20 PMID: 10640419
  9. Actin machinery: pushing the envelope.
    Curr Opin Cell Biol. 2000 Feb;12(1):104-12 PMID: 10679366
  10. Osteocyte function, osteocyte death and bone fracture resistance.
    Mol Cell Endocrinol. 2000 Jan 25;159(1-2):7-13 PMID: 10687847
  11. Adhesion to the extracellular matrix regulates the coupling of the small GTPase Rac to its effector PAK.
    EMBO J. 2000 May 2;19(9):2008-14 PMID: 10790367
  12. Cell coupling modulates the contraction of fibroblast-populated collagen lattices.
    J Cell Physiol. 2000 Jul;184(1):86-92 PMID: 10825237
  13. Regulation of the cytoskeleton and cell adhesion by the Rho family GTPases in mammalian cells.
    Annu Rev Biochem. 1999;68:459-86 PMID: 10872457
  14. Integrin engagement suppresses RhoA activity via a c-Src-dependent mechanism.
    Curr Biol. 2000 Jun 15;10(12):719-22 PMID: 10873807
  15. Signaling networks linking integrins and rho family GTPases.
    Trends Biochem Sci. 2000 Aug;25(8):388-91 PMID: 10916159
  16. Fibroblast-collagen-matrix contraction: growth-factor signalling and mechanical loading.
    Trends Cell Biol. 2000 Sep;10(9):362-5 PMID: 10932093
  17. Molecular mechanisms controlling actin filament dynamics in nonmuscle cells.
    Annu Rev Biophys Biomol Struct. 2000;29:545-76 PMID: 10940259
  18. Lysophosphatidic acid enhances collagen gel contraction by hepatic stellate cells: association with rho-kinase.
    Biochem Biophys Res Commun. 2000 Oct 14;277(1):72-8 PMID: 11027642
  19. Involvement of microtubules in the control of adhesion-dependent signal transduction.
    Curr Biol. 1996 Oct 1;6(10):1279-89 PMID: 8939572
  20. Extracellular matrix rigidity causes strengthening of integrin-cytoskeleton linkages.
    Cell. 1997 Jan 10;88(1):39-48 PMID: 9019403
  21. Tensegrity: the architectural basis of cellular mechanotransduction.
    Annu Rev Physiol. 1997;59:575-99 PMID: 9074778
  22. A micromachined device provides a new bend on fibroblast traction forces.
    Proc Natl Acad Sci U S A. 1997 Aug 19;94(17):9114-8 PMID: 9256444
  23. Cell locomotion and focal adhesions are regulated by substrate flexibility.
    Proc Natl Acad Sci U S A. 1997 Dec 9;94(25):13661-5 PMID: 9391082
  24. Rho GTPases and the actin cytoskeleton.
    Science. 1998 Jan 23;279(5350):509-14 PMID: 9438836
  25. The periodontal ligament: a unique, multifunctional connective tissue.
    Periodontol 2000. 1997 Feb;13:20-40 PMID: 9567922
  26. Tensional homeostasis in dermal fibroblasts: mechanical responses to mechanical loading in three-dimensional substrates.
    J Cell Physiol. 1998 Jun;175(3):323-32 PMID: 9572477
  27. Molecular dissection of the Rho-associated protein kinase (p160ROCK)-regulated neurite remodeling in neuroblastoma N1E-115 cells.
    J Cell Biol. 1998 Jun 29;141(7):1625-36 PMID: 9647654
  28. Activation of Rac and Cdc42 by integrins mediates cell spreading.
    Mol Biol Cell. 1998 Jul;9(7):1863-71 PMID: 9658176
  29. Integrin-mediated signals regulated by members of the rho family of GTPases.
    J Cell Biol. 1998 Jul 27;142(2):573-86 PMID: 9679153
  30. Microtubule depolymerization induces stress fibers, focal adhesions, and DNA synthesis via the GTP-binding protein Rho.
    Cell Adhes Commun. 1998 Jun;5(4):249-55 PMID: 9762466
  31. Regulation of the small GTP-binding protein Rho by cell adhesion and the cytoskeleton.
    EMBO J. 1999 Feb 1;18(3):578-85 PMID: 9927417
  32. Interactions between growth factors and gap junctional communication in developing systems.
    Novartis Found Symp. 1999;219:60-72; discussion 72-5 PMID: 10207898
  33. Bidirectional signaling between the cytoskeleton and integrins.
    Curr Opin Cell Biol. 1999 Apr;11(2):274-86 PMID: 10209151
  34. Separation of propulsive and adhesive traction stresses in locomoting keratocytes.
    J Cell Biol. 1999 May 3;145(3):589-604 PMID: 10225959
  35. Different contributions of microtubule dynamics and transport to the growth of axons and collateral sprouts.
    J Neurosci. 1999 May 15;19(10):3860-73 PMID: 10234018
  36. New depths in cell behaviour: reactions of cells to nanotopography.
    Biochem Soc Symp. 1999;65:15-26 PMID: 10320930
  37. Self-organization of tissue-equivalents: the nature and role of contact guidance.
    Biochem Soc Symp. 1999;65:27-42 PMID: 10320931
  38. The polarization of the motile cell.
    J Cell Sci. 1999 Jun;112 ( Pt 12):1803-11 PMID: 10341200
  39. Mechanotransduction in bone--role of the lacuno-canalicular network.
    FASEB J. 1999;13 Suppl:S101-12 PMID: 10352151
  40. Interplay between Rac and Rho in the control of substrate contact dynamics.
    Curr Biol. 1999 Jun 17;9(12):640-8 PMID: 10375527
  41. Integrin-mediated adhesion regulates cell polarity and membrane protrusion through the Rho family of GTPases.
    Mol Biol Cell. 2001 Feb;12(2):265-77 PMID: 11179414
  42. How do dendrites take their shape?
    Nat Neurosci. 2001 Apr;4(4):359-65 PMID: 11276225
  43. Nascent focal adhesions are responsible for the generation of strong propulsive forces in migrating fibroblasts.
    J Cell Biol. 2001 May 14;153(4):881-8 PMID: 11352946
  44. Force generation by cytoskeletal motor proteins as a regulator of axonal elongation and retraction.
    Trends Cell Biol. 2001 Jun;11(6):244-9 PMID: 11356360
  45. Collapsin response mediator protein switches RhoA and Rac1 morphology in N1E-115 neuroblastoma cells and is regulated by Rho kinase.
    J Biol Chem. 2001 Nov 16;276(46):43482-6 PMID: 11583986
  46. Transmembrane crosstalk between the extracellular matrix--cytoskeleton crosstalk.
    Nat Rev Mol Cell Biol. 2001 Nov;2(11):793-805 PMID: 11715046
  47. Myofibroblasts and mechano-regulation of connective tissue remodelling.
    Nat Rev Mol Cell Biol. 2002 May;3(5):349-63 PMID: 11988769
  48. Mechanisms of polarization of the shape of fibroblasts and epitheliocytes: Separation of the roles of microtubules and Rho-dependent actin-myosin contractility.
    Proc Natl Acad Sci U S A. 2002 Aug 6;99(16):10452-7 PMID: 12149446
  49. Modulation of fibroblast morphology and adhesion during collagen matrix remodeling.
    Mol Biol Cell. 2002 Nov;13(11):3915-29 PMID: 12429835
  50. Collagen substrata for studies on cell behavior.
    J Cell Biol. 1972 Sep;54(3):626-37 PMID: 4339818
  51. Cytoplasmic filaments and gap junctions in epithelial cells and myofibroblasts during wound healing.
    J Cell Biol. 1978 Mar;76(3):561-8 PMID: 564911
  52. Use and properties of ROCK-specific inhibitor Y-27632.
    Methods Enzymol. 2000;325:273-84 PMID: 11036610
  53. Fibroblasts contracting three-dimensional collagen gels exhibit ultrastructure consistent with either contraction or protein secretion.
    J Ultrastruct Res. 1982 Feb;78(2):178-92 PMID: 7201025
  54. The differentiation of the dermis in the laboratory mouse.
    Am J Anat. 1984 Feb;169(2):149-64 PMID: 6711458
  55. Analysis of the role of microfilaments and microtubules in acquisition of bipolarity and elongation of fibroblasts in hydrated collagen gels.
    J Cell Biol. 1984 Aug;99(2):536-49 PMID: 6146628
  56. Tension and compression in the cytoskeleton of PC 12 neurites.
    J Cell Biol. 1985 Sep;101(3):697-705 PMID: 2863274
  57. Cell-to-cell communication within intact human skin.
    J Clin Invest. 1988 Jul;82(1):248-54 PMID: 2455735
  58. Substrate for botulinum ADP-ribosyltransferase, Gb, has an amino acid sequence homologous to a putative rho gene product.
    J Biol Chem. 1988 Nov 25;263(33):17255-7 PMID: 3141419
  59. Fibroblast contractility and actin organization are stimulated by microtubule inhibitors.
    J Cell Sci. 1989 Jun;93 ( Pt 2):255-66 PMID: 2482296
  60. Three dimensional arrangement of fibrocytes in the dermal papilla of the human sole skin.
    Okajimas Folia Anat Jpn. 1990 Aug;67(2-3):195-202 PMID: 2216313
  61. Pseudopodial activity at the active edge of migrating fibroblast is decreased after drug-induced microtubule depolymerization.
    Cell Motil Cytoskeleton. 1991;19(3):152-8 PMID: 1878985
  62. Fibroblasts, myofibroblasts, and wound contraction.
    J Cell Biol. 1994 Feb;124(4):401-4 PMID: 8106541
  63. Inhibition of lysophosphatidate- and thrombin-induced neurite retraction and neuronal cell rounding by ADP ribosylation of the small GTP-binding protein Rho.
    J Cell Biol. 1994 Aug;126(3):801-10 PMID: 8045941
  64. Control of cytoskeletal mechanics by extracellular matrix, cell shape, and mechanical tension.
    Biophys J. 1994 Jun;66(6):2181-9 PMID: 8075352
  65. Rho, rac, and cdc42 GTPases regulate the assembly of multimolecular focal complexes associated with actin stress fibers, lamellipodia, and filopodia.
    Cell. 1995 Apr 7;81(1):53-62 PMID: 7536630
  66. A pre-loading method of evaluating gap junctional communication by fluorescent dye transfer.
    Biotechniques. 1995 Mar;18(3):490-7 PMID: 7779401
  67. Contraction due to microtubule disruption is associated with increased phosphorylation of myosin regulatory light chain.
    Proc Natl Acad Sci U S A. 1995 Oct 24;92(22):10252-6 PMID: 7479762
Article Info
Journal
Molecular biology of the cell
Abbr.
Mol Biol Cell
ISSN
1059-1524
DOI
10.1091/mbc.e02-08-0493
Email
frederick.grinnell@utsouthwestern.edu
Published
2003-02-00
Pages
384-95
Language
English
Region
United States
NLM ID
9201390
PMCID
PMC149979
Subset
IM
Grants
NIGMS NIH HHS · R01 GM031321 · United States
NIGMS NIH HHS · R37 GM031321 · United States
NIGMS NIH HHS · GM31321 · United States
External Links
PubMed source DOI: 10.1091/mbc.e02-08-0493 PMC Full Text View journal details
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